Studies on the hepatotoxicity of Amanita phalloides in the rat : II. Biochemical analysis of the lysosomal changes

Abstract

Marked changes in the integrity and fragility of liver lysosomes have been detected in rats poisoned with a lethal dose of a crude aqueous extract of Amanita phalloides. In the course of the poisoning, four lysosomal hydrolases (acid phosphatase, β- N-acetylglucosaminidase, β-galactosidase and β-glucuronidase) were found to undergo a progressive reduction in both their structure-linked latency and sedimentability. Concurrently, there occurred in the blood plasma a conspicuous increase of acid hydrolase activities, which distinctly preceded the subsequent increase of both aspartate aminotransferase and isocitrate dehydrogenase. Observations on the fractional free activity of the acid hydrolases at different substrate concentrations seem to rule out the possibility that a graded change in the permeability of the lysosomal membrane underlies the activation of lysosomal enzymes. Rather, activation seems to be an all-or-none kind of phenomenon. When submitted to various labilizing procedures in vitro, the liver lysosomal population from poisoned rats exhibited a modified fragility in comparison with control lysosomes. Factors such as the increased size of hydrolase-bearing particles, changes in the properties of the limiting membrane, or modifications in the intra as well as extralysosomal environment are likely to account for these results. The reliability of the observed lysosomal changes as indexes of the modifications that take place in vivo and the relevance of the latter to the production of the liver injury by Amanita phalloides are discussed.